Autoantigens are tissue components of an organism to which that organism directs an immune response. The condition which results from such a self-directed immune response is known as autoimmunity (or "autoallergy"). Proteins in or on sperm are known to be potent autoantigens, and autoimmunity to such proteins is believed a significant cause of infertility.
The rabbit sperm membrane autoantigen, RSA, is an essential sperm antigen which functions in fertilization. As a family of autoantigens which was originally isolated from rabbit epididymal sperm membranes and testis membrane pellets using a rabbit anti-rabbit sperm autoantibody immunoaffinity column, M. O'Rand and J. Porter, 122 J. Immunol. 1248 (1979), RSA consists of four low molecular weight protein staining bands of 14, 16, 17 and 18,000 apparent molecular weight. M. O'Rand et al., 129 Dev. Biol. 231 (1988). The ability to block the cytotoxic activity (sperm immobilization) of autoantiserum on live rabbit spermatozoa in the presence of complement is characteristic of the RSA family, M. O'Rand and J. Porter, 122 J. Immunol. 1248 (1979), as is its ability to form higher molecular weight aggregates, some of which are resistant to boiling, reduction and SDS treatment, M. O'Rand et al., 129 Dev. Biol. 231 (1988). RSA functions as a sperm lectin which binds the spermatozoon to the zona pellucida with high affinity (dissociation constant 5.6.times.10.sup.-13 M) and which can prevent spermatozoa from binding to zona-intact eggs, M. O'Rand et al. Id. Moreover, specific monoclonal and polyclonal anti-RSA antisera inhibit fertilization both in vivo and in vitro. M. O'Rand, 25 Biol. Reprod. 611 (1981); M.O'Rand et al., 30 Biol. Reprod. 721 (1984); M. O'Rand and G. Irons, 30 Biol. Reprod. 731 (1984).
The present invention arose from our continuing efforts to understand the molecular biology of sperm autoantigens. Specific objects of the present invention are to provide methods of diagnosing immune infertility in human subjects and to provide synthetic peptides useful for both diagnosing immune infertility and as immunocontraceptive agents.